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  • 1
    Publication Date: 2019
    Description: Abstract We use GPS data to show synchronization between the 2011 and 2016 drought cycle in California, accelerated uplift of the Sierra Nevada Mountains, and enhanced magmatic inflation of the Long Valley Caldera (LVC) magmatic system. The drought period coincided with faster uplift rate, changes in gravity seen in the Gravity Recovery and Climate Experiment (GRACE), and changes in standardized relative climate dryness index. These observations together suggest that the Sierra Nevada elevation is sensitive to changes in hydrological loading conditions, which subsequently influences the LVC magmatic system. We use robust imaging of horizontal GPS velocities to derive time‐variable shear and dilatational strain rates in a region with highly variable station distribution. The results show that the highest strain rates are near the eastern margin of the Sierra Nevada and western edge of the Central Walker Lane (CWL) passing directly through LVC. The drought period saw geographic shifts in the distribution in active shear strain in the CWL more than 60 km from the LVC, delineating the minimum extent over which the active magmatic system affects the CWL tectonic environment. We analyze declustered seismicity data to show that locations with higher seismicity rates tend to be (1) areas with higher strain rates and (2) areas in which strain rates increased during drought‐enhanced inflation. We hypothesize that drought conditions reduce vertical surface mass loading, which decreases pressure at depth in the LVC system, in turn enhances magmatic inflation, and drives horizontal elastic stress changes that redistribute active CWL strain and modulate seismicity.
    Print ISSN: 2169-9313
    Electronic ISSN: 2169-9356
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 2
    Publication Date: 2015-05-27
    Description: Real-time high-rate geodetic data have been shown to be useful for rapid earthquake response systems during medium to large events. The 2014 M w 6.1 Napa, California earthquake is important because it provides an opportunity to study an event at the lower threshold of what can be detected with GPS. We show the results of GPS-only earthquake source products such as peak ground displacement (PGD) magnitude scaling, centroid moment tensor (CMT) solution and static slip inversion. We also highlight the retrospective real-time combination of GPS and strong motion data to produce seismogeodetic waveforms that have higher precision and longer period information than GPS-only or seismic-only measurements of ground motion. We show their utility for rapid kinematic slip inversion and conclude that it would have been possible, with current real-time infrastructure, to determine the basic features of the earthquake source. We supplement the analysis with strong motion data collected close to the source to obtain an improved post-event image of the source process. The model reveals unilateral fast propagation of slip to the north of the hypocenter with a delayed onset of shallow slip. The source model suggests that the multiple strands of observed surface rupture are controlled by the shallow soft sediments of Napa Valley and do not necessarily represent the intersection of the main faulting surface and the free surface. We conclude that the main dislocation plane is westward dipping and should intersect the surface to the east, either where the easternmost strand of surface rupture is observed or at the location where the West Napa fault has been mapped in the past.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 3
    Publication Date: 2016-06-21
    Description: Near-global and continuous measurements from satellite altimetry have provided accurate estimates of global mean sea level in the past two decades. Extending these estimates further into the past is a challenge using the historical tide gauge records. Not only is sampling non-uniform in both space and time, tide gauges are also affected by vertical land motion (VLM) that creates a relative sea level change not representative of ocean variability. To allow for comparisons to the satellite altimetry estimated global mean sea level (GMSL), typically the tide gauges are corrected using glacial isostatic adjustment (GIA) models. This approach, however, does not correct other sources of VLM that remain in the tide gauge record. Here, we compare Global Positioning System (GPS) VLM estimates at the tide gauge locations to VLM estimates from GIA models, and assess the influence of non-GIA related VLM on GMSL estimates. We find that the tide gauges, on average, are experiencing positive VLM (i.e. uplift) after removing the known effect of GIA, resulting in an increase of 0.24 +/- 0.08 mm year −1 in GMSL trend estimates from 1900 to present when using GPS-based corrections. While this result is likely dependent on the subset of tide gauges used and the actual corrections used, it does suggest that non-GIA VLM plays a significant role in 20 th century estimates of GMSL. Given the relatively short GPS records used to obtain these VLM estimates, we also estimate the uncertainty in the GMSL trend that results from limited knowledge of non-GIA related VLM. This article is protected by copyright. All rights reserved.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 4
    Publication Date: 2016-05-28
    Description: Journal of the American Chemical Society DOI: 10.1021/jacs.6b01621
    Print ISSN: 0002-7863
    Electronic ISSN: 1520-5126
    Topics: Chemistry and Pharmacology
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  • 5
    Publication Date: 2015-07-07
    Description: Splice modulation therapy has shown great clinical promise in Duchenne muscular dystrophy, resulting in the production of dystrophin protein. Despite this, the relationship between restoring dystrophin to established dystrophic muscle and its ability to induce clinically relevant changes in muscle function is poorly understood. In order to robustly evaluate functional improvement, we used in situ protocols in the mdx mouse to measure muscle strength and resistance to eccentric contraction-induced damage. Here, we modelled the treatment of muscle with pre-existing dystrophic pathology using antisense oligonucleotides conjugated to a cell-penetrating peptide. We reveal that 15% homogeneous dystrophin expression is sufficient to protect against eccentric contraction-induced injury. In addition, we demonstrate a 〉40% increase in specific isometric force following repeated administrations. Strikingly, we show that changes in muscle strength are proportional to dystrophin expression levels. These data define the dystrophin restoration levels required to slow down or prevent disease progression and improve overall muscle function once a dystrophic environment has been established in the mdx mouse model.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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  • 6
    Publication Date: 2016-08-17
    Description: An onion-peeling technique is developed for inferring the emissivity profile of a stellarator plasma from a two-dimensional image acquired through a CCD or CMOS camera. Each pixel in the image is treated as an integral of emission along a particular line-of-sight. Additionally, the flux surfaces in the plasma are partitioned into discrete layers, each of which is assumed to have uniform emissivity. If the topology of the flux surfaces is known, this construction permits the development of a system of linear equations that can be solved for the emissivity of each layer. We present initial results of this method applied to wide-angle visible images of the Columbia Neutral Torus (CNT) stellarator plasma.
    Print ISSN: 0034-6748
    Electronic ISSN: 1089-7623
    Topics: Electrical Engineering, Measurement and Control Technology , Physics
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  • 7
    Publication Date: 2015-05-17
    Description: Journal of the American Chemical Society DOI: 10.1021/jacs.5b00275
    Print ISSN: 0002-7863
    Electronic ISSN: 1520-5126
    Topics: Chemistry and Pharmacology
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  • 8
    Publication Date: 2016-01-30
    Description: Large dsRNA molecules can cause potent cytotoxic and immunostimulatory effects through the activation of pattern recognition receptors; however, synthetic versions of these molecules are mostly limited to simple sequences like poly-I:C and poly-A:U. Here we show that large RNA molecules generated by rolling circle transcription fold into periodic-shRNA (p-shRNA) structures and cause potent cytotoxicity and gene silencing when delivered to cancer cells. We determined structural requirements for the dumbbell templates used to synthesize p-shRNA, and showed that these molecules likely adopt a co-transcriptionally folded structure. The cytotoxicity of p-shRNA was robustly observed across four different cancer cell lines using two different delivery systems. Despite having a considerably different folded structure than conventional dsRNA, the cytotoxicity of p-shRNA was either equal to or substantially greater than that of poly-I:C depending on the delivery vehicle. Furthermore, p-shRNA caused greater NF-B activation in SKOV3 cells compared to poly-I:C, indicating that it is a powerful activator of innate immunity. The tuneable sequence and combined gene silencing, immunostimulatory and cytotoxic capacity of p-shRNA make it an attractive platform for cancer immunotherapy.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 9
    Publication Date: 2016-02-14
    Description: Automatic estimation of velocities from GPS coordinate time series is becoming required to cope with the exponentially increasing flood of available data, but problems detectable to the human eye are often overlooked. This motivates us to find an automatic and accurate estimator of trend that is resistant to common problems such as step discontinuities, outliers, seasonality, skewness, and heteroscedasticity. Developed here, MIDAS is a variant of the Theil-Sen median trend estimator, for which the ordinary version is the median of slopes v ij =( x j –x i )/( t j –t i ) computed between all data pairs i 〉 j . For normally distributed data, Theil-Sen and least-squares trend estimates are statistically identical; but unlike least squares, Theil-Sen is resistant to undetected data problems. To mitigate both seasonality and step discontinuities, MIDAS selects data pairs separated by one year. This condition is relaxed for time series with gaps so that all data are used. Slopes from data pairs spanning a step function produce one-sided outliers that can bias the median. To reduce bias, MIDAS removes outliers and recomputes the median. MIDAS also computes a robust and realistic estimate of trend uncertainty. Statistical tests using GPS data in the rigid North American plate interior show ±0.23 mm/yr RMS accuracy in horizontal velocity. In blind tests using synthetic data, MIDAS velocities have an RMS accuracy of ±0.33 mm/yr horizontal, ±1.1 mm/yr up, with a 5th percentile range smaller than all 20 automatic estimators tested. Considering its general nature, MIDAS has the potential for broader application in the geosciences.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 10
    Publication Date: 2016-10-08
    Description: Bacteria occupy a diverse set of environmental niches with differing oxygen availability. Anaerobic environments such as mammalian digestive tracts and industrial reactors harbor an abundance of both obligate and facultative anaerobes, many of which play significant roles in human health and biomanufacturing. Studying bacterial function under partial or fully anaerobic conditions, however, is challenging given the paucity of suitable live-cell imaging tools. Here, we introduce a series of RNA-based fluorescent biosensors that respond selectively to cyclic di-GMP, an intracellular bacterial second messenger that controls cellular motility and biofilm formation. We demonstrate the utility of these biosensors in vivo under both aerobic and anaerobic conditions, and we show that biosensor expression does not interfere with the native motility phenotype. Together, our results attest to the effectiveness and versatility of RNA-based fluorescent biosensors, priming further development and application of these and other analogous sensors to study host–microbial and microbial–microbial interactions through small molecule signals.
    Keywords: Miscellaneous/other
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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